This invention relates to a nutritional formula having a balanced amino acid profile which is suitable for patients suffering from phenylketonuria.
Phenylketonuria (PKU) is an inherited defect of amino acid metabolism which results in an excess of phenylalanine (Phe) in the brain and plasma. If it is not detected and treated early in the life of an infant, the condition leads to irreversible damage of the nervous system, severe mental retardation and poor brain development. Once detected, the condition is treated by providing the infant, and later the child, with a low or Phe-free diet. Also, pregnant women who suffer from the condition are recommended a diet which is free from or low in Phe to avoid the risk of impairment of the development of the foetus and congenital malformation.
However a diet which is composed of natural foods and which is free from or low in Phe, eliminates many source of essential amino acids, vitamins and minerals. Consequently, without supplementation, such a diet would provide inadequate protein, energy, vitamins and minerals to support normal growth and development. Therefore it is common to use nutritional formulas to supplement the diets of PKU patients. Also, for babies, it is common to use infant formulas which have a low Phe content as the sole or primary food source.
Many formulas for PKU patients exist and are described in the literature. In most cases, they fall into two main categories. The first category comprises formulas produced from protein hydrolysates which have been subjected to activated charcoal or gel treatment to remove Phe. The formula disclosed in German patent 2117243 is an example of such a formula. The second category comprises formulas made up of mixtures of free amino acids. The formula disclosed in European patent application 0492138 is an example of such a formula.
The main problem with both types of formula is that they have an extremely bitter taste which is not completely masked by the additional ingredients of the formulas such as sugars. Consequently, it is often difficult to ensure that the patient consumes enough of the formulas to maintain required daily intakes of protein, amino acids, vitamins, minerals, and the like. This is particularly a problem with older children who may require up to 70g, dry weight, of the formulas per day. For example, Schuett, V. E.; 1990; DHHS Publication No HRS-MCH-89-5, reports that more than 40% of PKU patients in the US of eight years or older no longer adhere to the dietary treatment.
Various techniques for masking the bitter taste of the formulas have been attempted; quite often without complete success. For example, Keeskemthy et al; 1993; J Inherit. Metab. Dis.; 16(1), 111-118 discloses the use of gelatine capsules which contain the formula and hence mask the taste of the formula. However this is only really suitable for adult patients since it is often difficult to get infants and children to swallow capsules. Similar ideas are disclosed in International patent application WO 85/03230 and U.S. Pat. No. 5,393,532 which disclose coated tablets containing a low Phe formula. As an example of another approach, U.S. Pat. No. 5,411,757 discloses the supplementation of certain low Phe foods with certain L amino acids to provide nutritionally complete foods. The foods are described to be palatable. However the problem is that foods are not as versatile as formulas and are not always suitable for all patients.
Another approach to the problem has been the use of protein fractions which do not appear to have very bitter tastes. For example, the abstract of Japanese patent application J59-5111 describes the use of protein fractions obtained from albumin or milk whey albumin which are low in Phe and have improved taste. Another example is described in Japanese patent application JP4-12605 1. In this case, foods based upon K-casein macropeptides are mentioned as being suitable for PKU patients. However these protein fractions do not provide formulas with all essential amino acids. Further, Kitagawa et al; 1987; Enzyme; 38, 321-327 reports that no patients actually liked the formulas based on these protein fractions and most thought they were just as bad as the conventional formulations of the time.
It is therefore an object of this invention to provide a nutritional formula suitable for PKU patients which has improved taste and provides a substantially balanced amino acid profile but which is low in phenylalanine.
Accordingly, in one aspect, this invention provides a nutritional formula suitable as a complete diet for PKU patients, the nutritional formula comprising:
a protein source comprising caseino-glyco-macropeptide and complementary essential amino acids other than Phe to provide a balanced amino acid profile including an excess of Tyr;
a carbohydrate source;
a fat source; and
vitamins and minerals sufficient to meet daily requirements.
It is surprisingly found that supplementing caseino-glyco-macropeptide with essential amino acids other than Phe provides a protein source for a nutritional formula which has a good taste, a low osmolarity and a balanced amino acid profile. Further, the nutritional formula has a low Phe content which makes it ideally suited as a diet for PKU patients. The formula also provides an excess of Tyr to compensate for the inability of PKU patients to metabolise Phe into Tyr.
Preferably the protein source provides about 7% to about 13% of the energy of the nutritional formula; the fat source provides about 25% to about 55% of the energy of the nutritional formula; and the carbohydrate source provides about 40% to about 60% of the energy of the nutritional formula.
The protein source preferably comprises about 40% to about 60% by weight of caseino-glyco-macropeptide and about 60% to about 40% by weight of complementary amino acids.
In a further aspect, this invention provides a powdered nutritional formula suitable as a protein supplement for PKU patients, the nutritional formula comprising:
a protein source comprising caseino-glyco-macropeptide and complementary essential amino acids other than Phe to provide a balanced amino acid profile including an excess of Tyr; and
vitamins and minerals.
Preferably the protein source provides at least about 80% of the energy of the powdered nutritional formula; more preferably at least about 90%.
Further, the protein source preferably comprises about 40% to about 99% by weight of caseino-glyco-macropeptide and about 60% to about 1% by weight of complementary amino acids.
The complementary essential amino acids may be provided as a mixture of free amino acids and slow release capsules containing one or more poor tasting amino acids; for example Lys, Met, Trp and Val. The protein source preferably provides at least about 1.9 g His/16 gN; at least about 6.6 g Leu/16 gN; at least about 1.1 g Trp/16 gN; and at least about 3.1 g Tyr/16 gN.
In another aspect, this invention provides the use of caseino-glyco-macropeptide and complementary essential amino acids other than Phe in the preparation of a nutritional formula for PKU patients which has a balanced amino acid profile and an excess of Tyr.
In a further aspect, this invention provides a method of providing nutrition to a PKU patient, the method comprising enterally administering to the patient a nutritional composition which includes a protein source including caseino-glyco-macropeptide and complementary essential amino acids other than Phe to provide a balanced amino acid profile including an excess of Tyr; and vitamins and minerals.